Genetic Variant DAAM1:n.98C>A (chr14-59188743-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000556596.1(DAAM1):n.98C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,894 control chromosomes in the GnomAD database, including 2,267 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2253 hom., cov: 32)

Exomes 𝑓: 0.21 ( 14 hom. )

Consequence

DAAM1
ENST00000556596.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62

Publications

13 publications found

Variant links:

Genes affected

DAAM1 (HGNC:18142): (dishevelled associated activator of morphogenesis 1) Cell motility, adhesion, cytokinesis, and other functions of the cell cortex are mediated by reorganization of the actin cytoskeleton and several formin homology (FH) proteins have been associated with these processes. The protein encoded by this gene contains two FH domains and belongs to a novel FH protein subfamily implicated in cell polarity. A key regulator of cytoskeletal architecture, the small GTPase Rho, is activated during development by Wnt/Fz signaling to control cell polarity and movement. The protein encoded by this gene is thought to function as a scaffolding protein for the Wnt-induced assembly of a disheveled (Dvl)-Rho complex. This protein also promotes the nucleation and elongation of new actin filaments and regulates cell growth through the stabilization of microtubules. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2012]

DAAM1 links:

ENSG00000296267 (HGNC:):

ENSG00000296267 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2 link	c.-63C>A	5_prime_UTR_variant	Exon 1 of 25	ENST00000360909.8	NP_001257449.1	Q9Y4D1-2
DAAM1	XM_005267430.3 link	c.-63C>A	5_prime_UTR_variant	Exon 1 of 26		XP_005267487.1	Q9Y4D1-1
DAAM1	XM_005267431.2 link	c.-209C>A	5_prime_UTR_variant	Exon 1 of 26		XP_005267488.1	Q9Y4D1-1
DAAM1	XM_047431135.1 link	c.-209C>A	5_prime_UTR_variant	Exon 1 of 25		XP_047287091.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DAAM1	ENST00000556596.1 link	n.98C>A	non_coding_transcript_exon_variant	Exon 1 of 2	1
DAAM1	ENST00000360909.8 link	c.-63C>A	5_prime_UTR_variant	Exon 1 of 25	1	NM_001270520.2	ENSP00000354162.3	Q9Y4D1-2
DAAM1	ENST00000556135.1 link	c.-63C>A	5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000450498.1	G3V275
ENSG00000296267	ENST00000737689.1 link	n.*229C>A	downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23693

AN:

152082

Hom.:

2256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0481

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.150

GnomAD4 exome

AF:

0.206

AC:

143

AN:

694

Hom.:

Cov.:

AF XY:

0.192

AC XY:

AN XY:

458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.232

AC:

101

AN:

436

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.164

AC:

AN:

220

Other (OTH)

AF:

0.188

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.156

AC:

23676

AN:

152200

Hom.:

2253

Cov.:

AF XY:

0.156

AC XY:

11603

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0480

AC:

1994

AN:

41560

American (AMR)

AF:

0.110

AC:

1685

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

626

AN:

3472

East Asian (EAS)

AF:

0.157

AC:

811

AN:

5150

South Asian (SAS)

AF:

0.205

AC:

992

AN:

4830

European-Finnish (FIN)

AF:

0.246

AC:

2611

AN:

10598

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14424

AN:

67974

Other (OTH)

AF:

0.148

AC:

313

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1018

2036

3053

4071

5089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.197

Hom.:

4734

Bravo

AF:

0.141

Asia WGS

AF:

0.187

AC:

651

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

1.6

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over